Submitted on February 23, 2005
Revised on May 6, 2005
Accepted on May 7, 2005
Maternal genotype affects adult offspring environmental responses for lipid, obesity and diabetes phenotypes in LGXSM recombinant inbred strains
Joseph P. Jarvis, Jane Kenney-Hunt, Thomas H. Ehrich, L. Susan Pletscher, Clay F. Semenkovich, and James M. Cheverud
Department of Anatomy and Neurobiology, Washington University, St. Louis, MO 63110
Corresponding Author: jpjarvis{at}artsci.wustl.edu
Maternal effects occur because mothers sometimes provide an environment for their developing young. In mammals, this includes both the intra-uterine and the postnatal environment. While these effects are correctly environmental from the perspective of the offspring genome, their variance may have both a genetic and an environmental basis in the maternal generation. Here, reciprocal crosses between C57BL/6J and 10 LGXSM recombinant inbred (RI) strains were performed and litters were divided at weaning into high and low fat dietary treatments. Differences between reciprocal litters were used to measure genetic maternal effects on offspring phenotypes including growth, weekly body weights, organ and fatpad weights, fasting glucose level and response to a glucose challenge at 10 and 20 weeks, and adult serum levels of cholesterol, insulin, triglycerides, free fatty acids, and leptin. Nearly all traits show effects due to maternity (whether an individuals mother was from an RI strain or C57BL/6J). Many show strong maternity x strain interactions indicative of genetic variation in maternal effects across the RI strains. This variation allows mapping of the quantitative trait loci (QTL) involved. Though much of the literature on maternal effects relates to early life traits, we detect strong and significant maternal effects on traits measured on adult offspring which are associated with adult-onset chronic diseases such as obesity and diabetes mellitus (DM) in humans. In some cases, maternal effects accounted for as much as 10% of the trait variance despite being measured at least 17 weeks after direct mother-pup interactions ceased. We also explored the possibility that maternal effects interact with later environmental factors (dietary fat intake) to alter adult phenotypes; we found such an interaction with differences in maternal care between RI strain mothers and C57BL/6J mothers but not among the RI strain mothers themselves.